Autosomal Dominant Inheritance

Question 1

What are the clinical signs of achondroplasia?

Answer 1

Short stature, proximal limb shortening, trident hands, frontal bossing, kyphosis/lordosis, varus/valgus deformities

Question 2

What is the cause of achondroplasia?

Answer 2

Mutation in fibroblast growth factor receptor 3. 80% spontaneous mutations; associated with increased paternal age

Question 3

What are the clinical signs of Ehlers-Danlos syndrome?

Answer 3

Joint hypermobility/instability, easy bruising, skin hyperelasticity, valve disease, nerve compression disorders, sleep apnoea, (rare= blue sclera)

Question 4

What are the causes of Ehlers-Danlos syndrome?

Answer 4

Mutations in the fibrous proteins which make up collagen or the enzymes which alter it

Question 5

What is the cause of familial hypercholesterolaemia?

Answer 5

Mutation in LDL receptor gene or apolipoprotein B; does not bind properly and thus high LDL levels

Question 6

What is the cause of Huntingdon’s disease?

Answer 6

Too many (>36) trinucleotide repeats in the Huntingtin gene; located on the short arm of chromosome 4.

Question 7

What is the cause of Marfan’s disease?

Answer 7

Misfolding of fibrillin-1 (found in glycoproteins)- accumulation of TGF-B. Caused by mutations of FBN1 gene on chromosome 15

Question 8

What are the signs associated with myotonic dystrophy?

Answer 8

Muscle wasting, cataracts, heart conduction defects, endocrine changes, myotonia

Question 9

What is the cause of myotonic dystrophy?

Answer 9

DM1 is a trinucleotide repeat disorder of DMprotein kinase on chromosome 19. DM2 is a tetranucleotide repeat disorder of ZNF9 on chromosome 3